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Clinical data
Other namesTOK-001; VN/124-1; 17-(1H-Benzimidazol-1-yl)androsta-5,16-dien-3β-ol
Routes of
By mouth
  • (3S,8R,9S,10R,13S,14S)-17-(benzimidazol-1-yl)-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-ol
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.233.599 Edit this at Wikidata
Chemical and physical data
Molar mass388.555 g·mol−1
3D model (JSmol)
  • C[C@]12CC[C@@H](CC1=CC[C@@H]3[C@@H]2CC[C@]4([C@H]3CC=C4N5C=NC6=CC=CC=C65)C)O
  • InChI=1S/C26H32N2O/c1-25-13-11-18(29)15-17(25)7-8-19-20-9-10-24(26(20,2)14-12-21(19)25)28-16-27-22-5-3-4-6-23(22)28/h3-7,10,16,18-21,29H,8-9,11-15H2,1-2H3/t18-,19-,20-,21-,25-,26-/m0/s1

Galeterone (developmental code names TOK-001, VN/124-1) is a steroidal antiandrogen which was under development by Tokai Pharmaceuticals for the treatment of prostate cancer.[1] It possesses a unique triple mechanism of action, acting as an androgen receptor antagonist, androgen receptor down regulator,[2] and CYP17A1 inhibitor,[3] the latter of which prevents the biosynthesis of androgens.[4] As a CYP17A1 inhibitor, galeterone shows selectivity for 17,20-lyase over 17α-hydroxylase.[5]

Prostate cancer drug abiraterone and its analog galeterone are Δ5,3β-hydroxy steroids. Structures of these two agents are identical to endogenous steroid substrates (cholesterole, dehydroepiandorosterone and pregnenolone) for the 3β-hydroxysteroid dehydrogenase (3βHSD) of endocrine system. It has been reported that both of these agents are metabolized to 3-oxo-Δ4-steroids by 3βHSD in short period on oral administration. First metabolite 3-oxo-Δ4-abiraterone has more potent anti-prostate cancer properties than abiraterone where galeterone metabolite (3-oxo-Δ4-galaterone) has activity comparable to parent. Further these two metabolites undergo metabolism by 5α-reductase (5α-SRD) of endocrine system which leads to five more biologically inactive metabolites.[6] It is known that galeterone has poor oral bioavailability in rodents. Poor pharmacokinetic properties (oral absorption and metabolic half-life) of galeterone may be the reason for its clinical compromise.

Galeterone, along with abiraterone acetate, has been identified as an inhibitor of sulfotransferases (SULT2A1, SULT2B1b, SULT1E1), which are involved in the sulfation of dehydroepiandrosterone and other steroids and compounds, with Ki values in the sub-micromolar range.[7]

Clinical development[edit]

Galeterone was being compared to enzalutamide in a phase III clinical trial (ARMOR3-SV) for AR-V7-expressing metastatic castration-resistant prostate cancer.[8][9] Tokai announced the discontinuation of ARMOR3-SV on July 26, 2016, after a data monitoring committee determined that the trial was unlikely to meet its endpoint.[10] On August 22, 2016, the company announced the discontinuation of their phase II expansion (ARMOR2) as well.[11]

In August 2017, Tokai Pharmaceuticals discontinued the development of galeterone.[1] On December 17, 2018, it was announced that Educational & Scientific, LLC (ESL), in conjunction with University of Maryland ventures, would develop the drug.[12][13][14]


  1. ^ a b "Galeterone - Eledon Pharmaceuticals". AdisInsight. Springer Nature Switzerland AG.
  2. ^ Vasaitis T, Belosay A, Schayowitz A, Khandelwal A, Chopra P, Gediya LK, et al. (August 2008). "Androgen receptor inactivation contributes to antitumor efficacy of 17{alpha}-hydroxylase/17,20-lyase inhibitor 3beta-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene in prostate cancer". Molecular Cancer Therapeutics. 7 (8): 2348–2357. doi:10.1158/1535-7163.MCT-08-0230. PMC 2643345. PMID 18723482.
  3. ^ Handratta VD, Vasaitis TS, Njar VC, Gediya LK, Kataria R, Chopra P, et al. (April 2005). "Novel C-17-heteroaryl steroidal CYP17 inhibitors/antiandrogens: synthesis, in vitro biological activity, pharmacokinetics, and antitumor activity in the LAPC4 human prostate cancer xenograft model". Journal of Medicinal Chemistry. 48 (8): 2972–2984. doi:10.1021/jm040202w. PMID 15828836.
  4. ^ Brawer MK (2008). "New treatments for castration-resistant prostate cancer: highlights from the 44th annual meeting of the american society of clinical oncology, may 30-june 3, 2008, chicago, IL". Reviews in Urology. 10 (4): 294–296. PMC 2615106. PMID 19145273.
  5. ^ Yin L, Hu Q (January 2014). "CYP17 inhibitors--abiraterone, C17,20-lyase inhibitors and multi-targeting agents". Nature Reviews. Urology. 11 (1): 32–42. doi:10.1038/nrurol.2013.274. PMID 24276076. S2CID 7131777.
  6. ^ Alyamani M, Li Z, Berk M, Li J, Tang J, Upadhyay S, Auchus RJ, Sharifi N (July 2017). "Steroidogenic Metabolism of Galeterone Reveals a Diversity of Biochemical Activities". Cell Chemical Biology. 24 (7): 825–832.e6. doi:10.1016/j.chembiol.2017.05.020. PMC 5533090. PMID 28648378.
  7. ^ Yip CK, Bansal S, Wong SY, Lau AJ (April 2018). "Identification of Galeterone and Abiraterone as Inhibitors of Dehydroepiandrosterone Sulfonation Catalyzed by Human Hepatic Cytosol, SULT2A1, SULT2B1b, and SULT1E1". Drug Metabolism and Disposition. 46 (4): 470–482. doi:10.1124/dmd.117.078980. PMID 29436390.
  8. ^ Clinical trial number NCT02438007 for "A Study of Galeterone Compared to Enzalutamide In Men Expressing Androgen Receptor Splice Variant-7 mRNA (AR-V7) Metastatic CRPC" at
  9. ^ Silberstein JL, Taylor MN, Antonarakis ES (April 2016). "Novel Insights into Molecular Indicators of Response and Resistance to Modern Androgen-Axis Therapies in Prostate Cancer". Current Urology Reports. 17 (4): 29. doi:10.1007/s11934-016-0584-4. PMC 4888068. PMID 26902623.
  10. ^ "Tokai Pharmaceuticals Announces Clinical Update" (Press release). 26 July 2016.
  11. ^ "Tokai Pharma in flux with lead product candidate galeterone, enrollment in mid-stage prostate cancer study nixed; shares slump 23% after hours (NASDAQ:ELDN)". Seeking Alpha. 22 August 2016.
  12. ^ "Lowe inks new deal for clinical trials of another cancer drug". Stock Gitter.
  13. ^ "Educational & Scientific, LLC and University of Maryland, Baltimore Expand Relationship Through Licensing Agreement to Develop Novel Prostate Cancer Treatment". BioSpace. Retrieved 2019-04-03.
  14. ^ "Jamaica Observer: Lowe and Team Granted Licence for Further Development of Prostate Cancer Drug". Retrieved 2019-04-03.